Jonathan Steckbeck, PhD

Founder & CEO, Peptilogics

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Jonathan Steckbeck, PhD, MBA, is the founder and CEO of Peptilogics, a clinical-stage biotechnology platform company pioneering the development of best-in-class novel therapeutics. Under his leadership, Peptilogics has developed a computational drug discovery platform to speed the design and development of novel drugs across a range of therapeutic targets. The company is advancing a pipeline of novel therapeutics in focused indications and continually expanding the application of its platform to new disease areas.

Veronica Hall, PhD

Chief Operating Officer, Clarametyx Biosciences

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Veronica Hall, PhD, has a multidisciplinary background with more than 20 years of experience in life science research, including conception, design, and delivery of technical and commercialization solutions for vaccines, therapeutics, and drug/device combinations. Over the course of her career, Dr. Hall has successfully led R&D and partnership efforts, leading teams large and small for a range of small to mid-size biotech firms. She served as Senior Director at Emergent BioSolutions Inc. leading the strategic R&D pipeline growth. Dr. Hall received a Bachelor of Science in Biochemistry and Molecular Biology from University of California, Santa Cruz, and a Ph.D. in Biochemistry and Cellular Biology from Rice University. She completed her postdoctoral fellowship at the National Cancer Institute.

Matthew Henn

EVP R&D, Chief Scientific Officer, Seres Therapeutics

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Matthew Henn is Executive Vice President and Chief Scientific Officer at Seres Therapeutics. He has been involved in the discovery and development of multiple microbiome therapeutics across infectious, inflammatory, and oncology indications including VOWSTtm the first FDA-approved oral microbiota-based therapeutic. He has authored over 70 peer-reviewed publications; his research has focused on microbial populations and the functional role of microbes in both environmental and human disease applications, and also the development of genomic and functional tools to study these populations. Prior to helping launch Seres in 2012, he was the Director of Viral Genomics and Assistant Director of the Genome Sequencing Center for Infectious Diseases at the Broad Institute of MIT and Harvard. He has served on various NIH working groups on antimicrobial resistance and microbiome research, as a scientific advisor for the National Institutes of Health’s Viral Pathogen Bioinformatics Resource Center, as an ad-hoc reviewer and editor of various peer-reviewed journals, and as a scientific advisor to non-profit and for-profit organizations. He currently serves on the Board of Directors of the Microbiome Therapeutics Innovation Group and the scientific advisory board of Growcentia, Inc, an agricultural microbiome company. Dr. Henn is formally trained in ecology and evolutionary biology and earned his Ph.D. in ecosystem sciences from the University of California at Berkeley, where he was a NASA Earth Systems Sciences Fellow, and trained as a NSF Postdoctoral Fellow in Microbiology at Duke University.

Jong Lee, MBA

CEO & Cofounder, Day Zero Diagnostics

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Mr. Jong Lee is a co-founder and the CEO of Day Zero Diagnostics (DZD). DZD is developing a new class of infectious disease diagnostics for an era of growing antimicrobial resistance. The diagnostic platform incorporates proprietary technologies for ultra-high enrichment sample prep and sequencing data analysis to provide same day organism ID and AMR profiling directly from native samples. The platform will enable physicians to avoid prolonged empiric therapy and to switch to a targeted antimicrobial treatment within 8 hours rather than 2-5 days.

Prior to DZD, Jong spent two decades in strategy consulting focused on medical technology innovation in diabetes health care, cardiology, gastroenterology, and blood banking. He most recently served as the Senior VP of Marketing and Strategy for an early stage orthopedic company in joint arthroplasty.

Talk: Rapid Sequencing-Based Organism Detection and Antimicrobial Susceptibility Profiling for Clinical Diagnostics

Sequencing-based diagnostics are an emerging method for infectious disease testing that leverage an agnostic, metagenomic approach for the identification of pathogens. However, there are barriers to the realization of sequencing-based diagnostics for clinical decision making, including separation of signal from causative pathogens versus spurious signals caused by background commensals as well as from the up to billion-fold excess of human DNA. 

Blood2Bac™ is a rapid, culture-free, pathogen-agnostic sample preparation strategy that enriches bacterial and fungal DNA by up to 10 logs relative to human DNA from patient whole blood samples. This ultra high enrichment enables rapid whole genome sequencing (WGS) and computational analysis with a machine learning-based software package called Keynome^® to provide accurate species identification (ID) and antimicrobial susceptibility (AST) directly from whole blood at single digit CFU/mL pathogen concentrations in less than 8 hours.

The DZD assay demonstrates the ability to accurately identify a broad range of bacterial and fungal BSI pathogens at single digit CFU/mL concentrations, with data from 35 species included in the presentation. The majority of samples resulted in near complete genome recovery, with an average 1x coverage of 94.3% for bacteria and 99.3% for fungi.  We demonstrate a high specificity of 97.1% with just 3 false positive calls across 105 tested samples. AST testing was performed on 10 priority BSI strains, with a total of 109 AST predictions made on 47 individual bug/drug combinations.  Keynome gAST predictions were compared to phenotypic results and achieved 92.7% categorical agreement. Total turnaround time for Blood2Bac™ ultra high enrichment was an average of 5.77 hours and we previously demonstrated a singleplex time of a total of 2 hours for library preparation, ONT sequencing, and computational analysis.

The ability of Blood2Bac™ to rapidly recover whole pathogen genomes and for Keynome^® to provide accurate ID and AST predictions demonstrates the potential for integration of rapid, sequencing based diagnostics into clinical management of BSIs in the near future.

Dr. Justin Rolando, PhD

Research Fellow, Brigham and Women’s Hospital - Department of Pathology; Postdoctoral Fellow, Wyss Institute for Biologically Inspired Engineering; Research Fellow, Harvard Medical School.

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Dr. Rolando's research addresses a common challenge in human health: the inability to diagnose diseases early enough for effective treatment, especially when symptoms are latent or non-specific. Using liquid biopsy and longitudinal studies of human health, he seeks to diagnose nascent diseases. Specifically, using quantitative state-of-the-art single-molecule protein-based and nucleic acid-based diagnostic tools (e.g., SIMOA, LAMP, and CRISPR), predictive machine learning models, clinical imaging, and novel biomarkers, Justin uncovers the molecular mechanisms of how chemical heterogeneity leads to overarching organism-level phenomena like pediatric sepsis, cancer, and antimicrobial resistance. When developed further, the quantitative pathophysiological research from his teams identify fingerprints of disease, paving the way for reduced human morbidity and mortality through in vitro diagnostic systems.

Talk: Ultra-Sensitive Salivary Profiling: Insights into Infants Treated for Suspected Sepsis

Correctly identifying an infected infant to provide timely therapy without exposing a non-infected infant to unnecessary antibiotics remains a significant diagnostic challenge in neonatology. Early clinical symptoms of infection are subtle, nonspecific, or mirror symptoms commonly seen in the uninfected premature newborn. For this reason, “rule out sepsis” is one of the most common diagnostic tests in neonatal intensive care units. The Salivary Profiling for Infants Treated for Suspected Sepsis (SPITSS Trial) is an NICHD funded, ongoing, multi-center, prospective observational study aimed at determining the accuracy of an ultra-sensitive multiplexed salivary cytokine panel to correctly determine the infectious status of neonates using host-response biomarkers. This presentation will detail an interim analysis and the importance of ultra-sensitive measurements to show that neonatal saliva is a rich source of cytokines that can be noninvasively quantified to aid in clinical decision making.

Professor of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health

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Yonatan Grad is Professor of Immunology and Infectious Diseases at the Harvard TH Chan School of Public Health, and a member of the Division of Infectious Diseases at Brigham and Women’s Hospital. The Grad laboratory uses interdisciplinary methods—including molecular microbiology, pathogen genomics, and mathematical modeling—to study how pathogens evolve and spread through populations, with the motivation of improving clinical and public health strategies to decrease the burden of disease. A major theme of the lab’s work is antimicrobial resistance, with a particular focus on Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea.

Talk: Addressing AMR in Neisseria gonorrhoeae: the roles and challenges of diagnostics

Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, poses a global health threat with an increasing rate of infections and increasing antibiotic resistance. Timely and accurate diagnostics are paramount for effective management and control. However, most diagnosis is via nucleic acid amplification tests, which do not inform on antibiotic susceptibilities, and treatment is most commonly empiric ceftriaxone, the last line antibiotic. With strains now circulating globally that have reduced susceptibility to ceftriaxone and resistance or reduced susceptibility to all approved antibiotics, there is an urgent need for rapid diagnostics that can help tailor therapy. The microbial ecology and selective pressures acting on N. gonorrhoeae are also about to change with (1) the uptake of doxycycline post-exposure prophylaxis and (2) the recent report that a new antibiotic—zoliflodacin—successfully completed its Phase 3 trials for treatment of uncomplicated gonorrhea. In this talk, we will discuss the use of population genomics to help inform the development of new diagnostics, the potential impact of escape from sequence-based diagnostics for antibiotic susceptibility, and strategies around the implementation and monitoring for doxycycline post-exposure prophylaxis and zoliflodacin.

Mihaela Gadjeva, PhD

Associate Director, Moderna Theraputics

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Dr. Gadjeva is an internationally recognized immunologist with research interests in host-bacterial pathogenesis. She has an undergraduate and graduate degrees in Biochemistry from Sofia University, Bulgaria, and Oxford University, UK. After her postdoctoral training at Brigham and Women’s Hospital (BWH), Harvard Medical School, she rose through the Faculty ranks to an Associate Professor and maintained an NIH-funded lab for the past 12 years. Recently, Dr. Gadjeva joined Moderna Therapeutics where she leads bacterial vaccinology efforts. Her group applies system bacteriology and immunology approaches utilizing multiplexed quantitative proteomic and spatial transcriptomic analysis with the primary goal to discover key factors that determine outcomes of disease. The objective is to leverage this knowledge to discover novel therapeutic approaches to strengthen immunity during bacterial infections. Dr. Gadjeva has published more than 60 peer-reviewed scientific manuscripts and review articles in journals such as Nature Communications, Plos Pathogens, Immunity, Frontiers in Immunology, NEJM, etc.  Dr. Gadjeva’s contributions have been recognized by multiple awards such as First Place ARVO-AFER Merck Innovation award, Complement Society award, FOCIS award, BWH Innovation Award, ets. She also serves as an adviser to the Biotechnology Graduate Degree program at Harvard University.

Talk: Towards generation of an integrated map of infection

As there is a strong need to develop intervention strategies against ESKAPE pathogens, there is a great interest in developing new approaches that will bring depth to our understanding of the biology of these pathogens. I will discuss our efforts at developing comparative genomics and transcriptomics approaches to generate unified host-pathogen maps of infection which will ultimately lead to intervention opportunities. Genomic data from P. aeruginosa and E. coli clinical isolates were collected from the past 20 years and analyzed using comparative genomics to elucidate changes in the core genomes and frequencies of AMR acquisition. The analysis pointed to a staggering 40% increase in the appearance of AMR resistance traits in the clinical strains, tendencies that necessitate rapid interventions. To gain insights into the pathogen behavior within the infected tissues, we developed spatial, pathogen-specific transcriptome profiling and found differential enrichment of pathogen-specific transcripts at distinct anatomical locations. By using machine learning approaches, we correlated pathogen transcriptional features to host responses and found interconnected circuits. Cumulatively, our data highlight coordinated spatial and temporal transcriptional interplay between host and that may pinpoint to druggable circuits. 

Jared Kehe, PhD

Co-founder & Chief Scientific Officer, Concerto Biosciences

A passionate biotechnologist with expertise in microbial ecology, microbiome science, and microfluidics, Jared is Co-founder and Chief Scientific Officer of Concerto Biosciences, a Boston-based startup that designs microbial products. Jared co-invented Concerto’s platform, kChip, a discovery engine that physically constructs millions of miniature, defined microbial communities simultaneously. By observing the behavior of these communities, Jared’s team rapidly identifies promising microbial, prebiotic, and postbiotic product candidates. Aiming to unleash a new era of microbial research, Jared oversees discovery projects spanning skin health, vaginal health, gut health, agriculture, and food science. Jared holds a PhD in Biological Engineering from MIT (NSF Fellow, Presidential Fellow), where he worked with Prof. Paul Blainey to develop kChip and apply it to foundational questions in microbial ecology.

Talk: Post-Pathogen: How Microbial Ecology-Based Interventions Can Pacify—Rather than Kill—Our Symbionts

Antibiotics, crucial for combatting life-threatening infections, ironically create the very pathogens we seek to eradicate: Beyond selecting for antimicrobial resistance, antibiotics kill virulence-suppressing commensal microorganisms and disrupt host immunity. The healthy microbiome, composed of the diverse microbes that co-evolved symbiotically alongside humans, placate would-be pathogens and resist their colonization. Designing antibiotic alternatives or infection preventatives that recreate this microbiome-endowed protection requires an unprecedented understanding of how microbes behave together. Concerto unlocks this knowledge with kChip, a discovery engine that physically constructs millions of miniature, defined microbial cocultures simultaneously. By observing the behavior of a pathogen within each coculture, Concerto rapidly identifies the most promising microbial combinations, prebiotics, and postbiotics for development into new products. In our first endeavor, Concerto constructed >6 million communities of skin-dwelling microbes to discover an “ensemble” of bacteria that pacifies pathogenic S. aureus. We have since initiated discovery projects in vaginal health, gut health, and agriculture. In partnership with a diverse array of biotech and biopharma companies, Concerto aims to vastly improve our understanding of microbial ecology and develop durable alternatives to traditional antibiotics.

Janira Prichula, PhD

Postdoctoral Research Fellow at Gilmore’s Lab, Harvard Medical School/ Massachusetts Eye and Ear

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I am a postdoctoral research fellow currently working in the Gilmore Lab, Harvard Medical School/ Massachusetts Eye and Ear, Boston, with interest in genomics related to antibiotic resistance. I had the opportunity to conduct research on the global distribution of enterococci and antibiotic resistance genes in marine environments in remote ecologies of Patagonia and other regions of South America during my Master's and Ph.D. research. These experiences have shown me that understanding how bacteria relate to their hosts, what traits are central to colonization, and determining where reservoirs of resistant strains occur will provide critical information for preventing and managing the problem of multidrug-resistant bacteria infection. Currently, I am studying new approaches for the control of enterococcal infection. 

Talk: Efagins – A New Class of Phage-derived Anti-enterococcal Agents

Enterococci are leading causes of multidrug-resistant hospital infections. Here we identify a new potentially therapeutically useful bactericidal agent for treating enterococcal infections we term efagins.  Efagins appear to represent a new type of anti-enterococcal entity that evolved from elements of phages, with antibacterial properties – E. faecalis phage-derived bacteriocins. They appear to be unique to the species E. faecalis, and are encoded as part of the core chromosome of that species. Their antibacterial property, however, extends to other enterococcal species and possibly broader. Clues to the mechanism of bacterial killing derived from examination of polymorphisms in the efagin operon. The genes for efagin are clustered in the chromosome of E. faecalis and are highly conserved, indicating that it is under selection and is important to the biology of that species. However, the 3’ end of one of the genes associated with efagin expression is unusually polymorphic. This polymorphism was observed to co-vary with polymorphisms in another region of the E. faecalis chromosome that encodes the E. faecalis homolog of wall teichoic acid, termed “enterococcal polysaccharide antigen” or EPA. Experimentally, we found that the efagin encoded by one strain of E. faecalis is not effective against the producing strain, but is effective against other strains of E. faecalis with different EPA content. Structural modeling showed that the polymorphic efagin gene within was related to that encoding a tail fiber of a Listeria phage that bound the listeria cell wall polysaccharide. Moreover, the polymorphisms occurring within the efagin could be mapped to polysaccharide binding sites within the listeria phage tail fiber. From comparing genome sequences of thousands of E. faecalis strains, we believe that there are 6-8 natural variations in efagins with alterations in the cell wall carbohydrates they target. That efagins target non-homologous strains indicates they play a natural role in defense. That they target the cell wall polysaccharide of other E. faecalis strains suggests that the defense is against ecological displacement by the other E. faecalis lineages. That the activity extends to some other enterococcal species indicates that this defense may be somewhat broader than only against other E. faecalis strains. By TEM, efagins appear to be phage tail-like particles of ~ 160 nm in contour length. Other evolved phage-derived antibacterial factors have been described from a few other types of bacteria, but none are closely related to efagins, and so far, no other bacterial species has been identified where these elements are part of the core chromosome of that species.

Poster presentation: VE707, a Defined Live Biotherapeutic Product for Prevention of Infection by Multidrug-Resistant Gram-Negative Bacteria

Gregory Medlock, Cintia Felix, Wajd Alsharif, Louis Cornacchione, Matthew Schinn, Sue Bedard-Shurtleff, Jason Norman, Jeremiah Faith, Ed Kuijper, Bernat Olle, and Silvia Caballero

Background: Infections with multidrug-resistant organisms (MDRO) are increasing at an alarming rate in hospitals worldwide. MDRO infections are often preceded by asymptomatic intestinal colonization and proliferation by the MDRO. Treatments such as non-absorbable antibiotics and fecal microbiota transplantation (FMT), which decrease the abundance of MDRO in the intestines, have shown efficacy at preventing MDRO infection. Despite the success of FMT at reducing intestinal MDRO abundance without leading to resistance, FMT composition and efficacy is variable and its safety profile questionable. This highlights the need for a defined microbiome-based product with robust efficacy and standardized manufacturing.

Methods: VE707 is a defined live biotherapeutic product (LBP) consisting of a consortium of bacterial strains that reduce intestinal carriage of carbapenem-resistant and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (Kpn) and Escherichia coli (Eco). Using a top-down approach, we characterized fecal material from healthy individuals for their ability to suppress Kpn and Eco ex vivo and in vivo, then identified donor material enriched for activity against both pathogens. Next, we used in vitro, in vivo, and bioinformatic approaches to design defined LBPs using the bacterial strains from this donor based on their anti-MDRO activity. We evaluated the ability of these LBPs to reduce Kpn and Eco abundance in a mouse co-colonization model.

Results: Of 94 LBPs designed and evaluated which each consisted of between 7 and 50 strains, VE707 showed the greatest activity, as demonstrated by a > 3-log10 reduction in Kpn and Eco in stool (Figure 1; p = 0.0022). Furthermore, VE707 was active in vitro against a panel of 40 MDR Kpn and Eco clinical isolates (> 2-log10 reduction in Kpn and Eco growth, p < 0.05). We have developed a co-culture process to enable commercially feasible manufacturing of VE707 and found that VE707 produced via co-culture has in vivo anti-MDRO activity equivalent to VE707 produced via monoculture (Figure 1; > 3-log10 reduction in Kpn and Eco in stool, p = 0.0022).

Conclusions: Our results show that VE707, a defined bacterial consortium with broad anti-MDRO activity, is successful at decolonizing Kpn and Eco and can be manufactured efficiently with a co-culture process.

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Presenting author: Greg Medlock

Director, Vedanta Biosciences

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